JAIDS Journal of Acquired Immune Deficiency Syndromes:
Letters to the Editor
Origin and Outbreak of HIV-1 CRF55_01B Among MSM in Shenzhen, China
Zhao, Jin PhD*; Cai, Wende MD*; Zheng, Chenli BSc*; Yang, Zhengrong PhD*; Xin, Ruolei PhD†; Li, Guilian BSc*; Wang, Xiaohui PhD*; Chen, Lin MD*; Zhong, Ping PhD‡; Zhang, Chiyu PhD§
*HIV/AIDS Prevention and Control Division, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
†Department of AIDS and STD, Beijing Center for Disease Control and Prevention, Beijing, China
‡Department of AIDS and STD, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
§Pathogen Diagnostic Center, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Supported in part by grants from the National Natural Science Foundation of China (81270043, 81071391, and 30901224), Key Scientific and Technological Program of China, and National Science and Technology Major Project for Infectious Disease Control and Prevention (2012ZX10001-002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.
The authors have no conflicts of interest to disclose.
To the Editors:
Fifty-eight HIV-1 circulating recombinant forms (CRF) have been identified worldwide and some of them did not cause epidemic since identification.1 In China, early cocirculation of 2 HIV-1 subtypes B and C among injection drug users (IDUs) had led to the generation of CRF07_BC, CRF08_BC, and a large number of unique recombinant forms.2 After origin, CRF07_BC and CRF08_BC rapidly spread to other regions of China (eg, Xinjiang, Liaoning, Guangxi, Jiangsu, etc.) through drug trafficking routes and cause outbreak among IDUs.3–5
Apart from IDUs, men who have sex with men (MSM) are also the high-risk group contributed to the global spread of AIDS.6 Recent years, there is a clearly increasing trend of HIV prevalence among MSM in some big cities (eg, Beijing, Shanghai, Guangzhou, Shenzhen, Shengyang, Chongqing, and Chengdu) of China,7–11 and 3 HIV-1 subtypes B, C, and CRF01_AE were rapidly mixed among MSM and formed cocirculation,12 which favors the generation of new HIV-1 recombinants among these subtypes. Several CRFs derived from CRF01_AE and B had been identified among MSM in other countries in Asia (eg, Malaysia and Thailand); however, some of these CRFs did not lead to an epidemic.1 In 2012, a new recombinant between CRF01_AE and B was identified as CRF55_01B among MSM in China, becoming the third CRF being found in China.13 When and where CRF55_01B originated and whether it causes an outbreak among MSM or other high-risk groups like CRF07_BC and CRF08_BC among IDUs deserve investigation.
Shenzhen is located in the southern coast of China and borders with Hong Kong. As the earliest open city, it has developed into one of the most successful economic regions in China. The postmodern culture and humanistic environment provide an ideal region to attract a large number of young people from all over the country to work, live, and consume in Shenzhen, which objectively forms a favorable living space for about 70,000 MSM in Shenzhen. HIV-1 prevalence among MSM in Shenzhen has increased from 0.9% in 2002 to 6.7% in 2008, and 10.3% in 2011. From 2006 to 2013, we collected 4931 HIV-1–seropositive blood samples from MSM and heterosexuals in Shenzhen, and 40% of MSM were recently infected with HIV-1. From them, we obtained 1072 pol sequences for HIV subtyping. A total of 99 CRF55_01B were identified, accounting for 9.2% of all subtyped sequences. The CRF55_01B sequences, including 99 from Shenzhen, 3 from Shanghai, and 1 from Beijing, are available under GenBank accession numbers KF857358-KF857460. Majority of CRF55_01B (84.8%) were circulating among MSM, significantly higher than those in heterosexuals (P = 0.025, χ2 test) (Figure 1A). Of particular importance, the earliest sample carrying CRF55_01B was traced back to 2007, indicating that CRF55_01B had a relative long history among MSM in Shenzhen, and suggesting that it might originate here.
The maximum clade credibility tree of CRF55_01B shows that CRF55_01B from Shenzhen MSM are located at the root of the tree, and strains from heterosexuals and other high-risk groups are dispersed within the strains from MSM (Figure 1B). The ancestral state reconstruction indicates that Shenzhen MSM is the origin of CRF55_01B (posterior probability = 0.99) (data not shown). These support that CRF55_01B initially originated among MSM in Shenzhen and rapidly spread to heterosexuals. In addition, 3 representative strains for definition of CRF55_01B, which were isolated from MSM in Changsha city of Hunan province and Dongguan city of Guangdong province,13 and 3 strains from MSM in Shanghai, are dispersed within the Shenzhen MSM sequences. Furthermore, 1 CRF55_01B sequence isolated from MSM in Beijing, the capital of China, also clustered within the Shenzhen MSM sequences in maximum likelihood tree (data not shown). These indicate that CRF55_01B has spread to other regions of China through floating MSM.
The evolutionary rate, the time to the most recent common ancestor (tMRCA), and the demographic history of CRF55_01B were inferred using BEAST v1.7.5. The evolutionary rate for CRF55_01B pol fragment was estimated to be 1.44 × 10−3 [95% highest posterior density (HPD), 6.88 × 10−4 to 2.21 × 10−3] nt substitutions/site/year, consistent with the order of magnitude of 10−3 expected for HIV-1. The estimated coefficient of rate variation was 0.80 (95% HPD, 0.49–1.12), indicating that there is significant rate variation among lineages, and suggesting that a relaxed molecular clock model should be used to construct the time-scale of the CRF55_01B clade. The tMRCA of CRF55_01B was inferred to be 2001.0 (95% HPD: 1996.2–2004.5), implying the origin time of the CRF55_01B. The Bayesian skyline plot shows that HIV-1 CRF55_01B experienced an initial phase of fast exponential growth during 2006–2009 and then remained stable (Figure 1C). The exponential growth coalescent model indicates that the CRF55_01B expanded during 2006–2009 with a mean growth rate of 0.66 per year (95% HPD: 0.33–1.03). The demographic trend of CRF55_01B was consistent with the prevalence pattern of CRF55_01B in Shenzhen (Figure 1A). The earliest detection of CRF55_01B among Shenzhen MSM in 2007 might also reflect the fast exponential growth during this period.
As a young city, the average age of Shenzhen population is 30 years, and about 80% of them are temporary or floating population (from the 2010 Shenzhen demographic census data, available at http://www.sztj.gov.cn/xxgk/tjsj/pcgb/201105/t20110512_2061597.htm). Among 70,000 MSM in Shenzhen, 90% were floating population coming from all over the country (including 5%–10% from Hong Kong), and 50% have stayed in Shenzhen for less than 1 year.14 This implies that Shenzhen has become the most important gathering place for MSM from all over the country, and this huge group of floating MSM in Shenzhen will serve as an important vehicle for transmission of HIV-1 CRF55_01B and even other subtypes from Shenzhen to other regions of China. Furthermore, majority of Chinese MSM engage in bisexual behaviors,15 which provides more chance for CRF55_01B transmission from MSM to heterosexuals through their female partners. We detected 1 CRF55_01B strain from Shenzhen heterosexuals sampled in 2007, indicating that the MSM-to-heterosexuals transmission of CRF55_01B occurred very soon after its generation (Figure 1B). In summary, we predict that CRF55_01B will become a new HIV-1 recombinant most commonly transmitted among MSM after the prevalence of CRF07_BC and CRF08_BC among IDUs in China. Recently, sporadic detection of CRF55_01B in Dongguan, Hunan, Shanghai, and Beijing might be a prelude of CRF55_01B outbreak among MSM in these city/provinces and even other regions of China in the near future.
The authors thank all participants, peer workers, and the staff of the medical key laboratory of Guangdong and Shenzhen for sample preparation and testing.
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© 2014 by Lippincott Williams & Wilkins
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